UMLS:C0019158 - FACTA Search

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Query: UMLS:C0019158 (hepatitis)
30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma is one of the most common cancers worldwide. Epidemiologic studies shows a striking correlation between areas where this tumor is prevalent and where hepatitis virus B and C are endemic, contaminations of food with mycotoxin aflatoxin B1, excessive alcohol intake, prolonged cigarette smoking, sexual hormones. Combination of chemical, physical, and genetic insults to individual hepatocytes involve changes in the genome transformed or neoplastic cell, depending to both the activation of oncogenes (e.g., ras) and the inactivation of tumor supressor genes (e.g., p53). Advances in radiologic techniques such as ultrasonography, computed tomography, angiography and dosages of tumor markers like alpha-fetoprotein offers still the best for diagnosis and screening for hepatocellular carcinoma. Then the diagnosis has become possible during the early stages, characterized to be a very well-differentiated tumour that has returned its preexisting liver structure, with a certain proportion have a multicentric origin. Hepatocellular carcinoma carries an extremely poor prognosis, with a median survival between 2-4 weeks, for those without treatment. Surgical resection are the only curative modality for this disease. In these patients two main patterns of intrahepatic recurrence after hepatectomy are defined, and depends on the growth of residual satellite tumours or synchronous and metachronous multicentric carcinogenesis. This evolution is estimated to be nearly 50%, with 5-year survival rate of nearly 30%. The presence of cirrhosis, satellite nodules, venous invasion, the absence of capsule formation and positive surgical margin (< or = 5 mm) were associated with higher intrahepatic recurrence rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Small hepatocellular carcinoma. New concepts on intrahepatic recurrence after hepatectomy in orthotopic liver transplantation]. 757 79

Interactive hepadnaviral and chemical hepatocarcinogenesis was studied in woodchucks inoculated as newborns with woodchuck hepatitis virus (WHV), which is closely related to the human hepatitis B virus. When the woodchucks reached 12 months of age, aflatoxin B1 (AFB1) was administered in the diet at dose levels of 40 micrograms/kg body weight/day for 4 months and subsequently 20 micrograms/kg body weight/day (5 days/week) for lifetime. WHV DNA was demonstrated by Southern blot hybridization in the serum and by PCR in the serum and/or liver tissue. The histo- and cytomorphology of the liver were investigated by light and electron microscopy. WHV carriers with and without AFB1 treatment developed a high incidence of preneoplastic foci of altered hepatocytes, hepatocellular adenomas, and hepatocellular carcinomas that appeared 6-26 months after the beginning of the combination experiment. Administration of AFB1 to WHV carriers resulted in a significantly earlier appearance of hepatocellular neoplasms and a higher incidence of hepatocellular carcinomas compared to WHV carriers not treated with AFB1. Neither hepatocellular adenomas nor carcinomas (but preneoplastic foci of altered hepatocytes) were detected in woodchucks receiving AFB1 alone, and no preneoplastic or neoplastic lesions were found in untreated controls. These results provide conclusive evidence of a synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary AFB1. Except for the frequent presence of ground glass cells containing surface antigen filaments in the infected woodchucks, the phenotype of preneoplastic foci of altered hepatocytes was similar in WHV carriers with and without exposure to AFB1 and in animals treated with AFB1 alone. Clear cell foci excessively storing glycogen and/or fat, amphophilic cell foci crowded with mitochondria and peroxisomes, and mixed cell foci composed of various cell types including basophilic cells rich in ribosomes predominated. The cellular phenotype in neoplastic lesions varied from clear, amphophilic, and mixed cell populations in highly differentiated adenomas and carcinomas to basophilic cell populations prevailing in poorly differentiated carcinomas. The striking similarities in altered cellular phenotypes of preneoplastic hepatic foci emerging after both hepadnaviral infection and exposure to AFB1 suggest closely related underlying molecular mechanisms that may be mainly responsible for the synergistic hepatocarcinogenic effect of these oncogenic agents.
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PMID:Synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary aflatoxin B1 in woodchucks. 761 67

Liver DNA specimens from woodchucks kept in captivity, 10 naturally infected with hepatitis virus (WHV) and five WHV-free, were examined for the presence of carcinogen-DNA adducts by 32P-postlabeling. The number of adducts was significantly higher in WHV carriers than in uninfected animals, and the total amounts of adducts per 10(9) nucleotides were also considerably enhanced by WHV infection, when using both butanol extraction (22.2 +/- 7.1 vs. 12.6 +/- 2.8, means +/- S.D.) and nuclease P1 enrichment (8.5 +/- 5.9 vs. 2.8 +/- 1.7). Two individual adducts were also significantly higher in WHV carriers. No significant variation occurred as related to age, sex or time length of captivity. These findings are consistent with our previous studies supporting an enhanced metabolism of chemical hepatocarcinogens in both human and woodchuck hepadnavirus infections. Several significant and remarkable correlations were pointed out by relating DNA adduct data to more than 30 virological, histopathological and metabolic parameters which had been previously evaluated in the same animals. For instance, numbers and/or levels of adducts were positively related to the amounts of virus present in hepatocytes, to cell damage (gamma-glutamyltranspeptidase activity), to the severity of the liver histopathological picture, and to monooxygenase activities, while they were inversely related to cellular glutathione concentrations and to detoxification of the direct-acting mutagen 4-nitroquinoline 1-oxide. The major adduct significantly correlated with the metabolic activation of the aromatic amine 2-aminofluorene and of the heterocyclic amines 3-amino-1-methyl-5H-pyrido(4,3)indole (Trp-P-2) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), whereas another adduct significantly correlated with the metabolic activation of the mycotoxin aflatoxin B1. Thus, the enhanced metabolism of chemical hepatocarcinogens and the increased formation of carcinogen-DNA adducts in the liver of WHV carriers appear to represent one of the mechanisms contributing to the association between chronic hepadnavirus infection and development of primary hepatocellular carcinoma.
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PMID:Enhanced levels of DNA adducts in the liver of woodchucks infected with hepatitis virus. 767 44

Day-old broiler chicks found negative for maternal antibodies against inclusion body hepatitis (IBH) virus by agar gel precipitation test and viral antigen in cloacal swabs by dot enzyme immunoassay were divided into 6 groups of 20 chicks each. Group A was fed aflatoxin B1 at 1.25 ppm from 3 to 38 days of age; group O was fed ochratoxin A at 0.5 ppm from 3 to 38 days of age; group V was inoculated with 1 ml of IBH virus of titre log10 6.5 EID50 per 0.2 ml. Groups AV and OV were given aflatoxin B1 and ochratoxin A, respectively, and also infected with the virus. Group C served as control. There was mild enlargement and paleness of the liver up to 18 days post inoculation in group V; there were no lesions in group A; and there was gradual enlargement of the kidneys from 10 days post feeding of mycotoxin onwards in group O. In the combined groups AV and OV the gross lesions were slightly more severe. In group V, varying degrees of degenerative histopathological changes, congestion and haemorrhages were seen particularly in the liver, followed by the kidneys, bursa, spleen, myocardium and lungs, along with intranuclear inclusion bodies in the hepatocytes, mostly in the early stages of infection. Similar microscopic changes, but without inclusion bodies, were seen in groups A and O and the changes were pronounced in the later stages. In group O, the kidney lesions were more pronounced than the liver lesions. In the concurrently infected groups, AV and OV, the changes were similar but slightly more marked than in the corresponding individual groups. Inclusion bodies in hepatocytes were more frequent, more prominent and appeared earlier in the concurrent groups.
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PMID:Pathological studies in broiler chicks fed aflatoxin or ochratoxin and inoculated with inclusion body hepatitis virus singly and in concurrence. 776 37

Synergy between exposure to chemical carcinogens (nitrosamines) and infestation with the liver fluke Opisthorchis viverrini has been demonstrated in a hamster model of hepatocarcinogenesis (Flavell et al., Carcinogenesis 4:927-930, 1983; Thamavit et al., Carcinogenesis 8:1351-1353, 1987). To elucidate the mechanisms of this interaction we tested the hypothesis that liver parasitism might influence the expression and activity of carcinogen metabolizing enzymes. We found that one, and perhaps more, hamster liver cytochrome P450 (CYP) isozymes immunorelated to mouse CYP2A5 contributed up to 50 or 60% of the hepatic aflatoxin B1 (AFB) and N-nitrosodiethylamine (NDEA) metabolism, respectively. As inferred from average enzyme activities and from western blot, immunoinhibition, and substrate (coumarin) inhibition analyses, O. viverrini infestation increased the expression of enzymes detectable by anti-CYP2A5 antibody as well as NDEA metabolism in male but not in female hamsters. Immunohistochemical analysis of CYP2A expression by anti-mouse CYP2A5 antibody demonstrated that the O. viverrini-associated increase was not uniformly distributed throughout the liver but occurred in hepatocytes immediately adjacent to areas of inflammation. Immunohistochemical analysis of AFB-DNA adducts in the livers of O. viverrini-infested hamsters treated with AFB showed that the highest levels of adducts were found in the regions of liver where hepatocellular expression of enzymes detectable by anti-CYP2A5 antibody is induced. These results suggest that a high local expression of CYP isozymes in O. viverrini-infested livers could be a contributing risk factor in the development of liver cancers associated with parasitic hepatitis.
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PMID:Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome P450 and carcinogen metabolism in male hamster liver. 791 96

Infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (HCC) both in humans and in animals. Recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human HCCs, predominantly from hepatitis B virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. To determine whether p53 mutations are common to HCCs of hosts infected with related hepadnaviruses with and without treatment with aflatoxin, we studied the occurrence of mutations in the p53 gene in HCCs of ground squirrels and woodchucks with history of infection with ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus, respectively. Sequencing of wild type p53 genes from ground squirrels and woodchucks revealed remarkable homology between the two species with only a few amino acid differences in exons 4, 8, and 9. Using direct polymerase chain reaction sequencing, we analyzed the state of the p53 gene (exons 4-9) in 20 HCCs from ground squirrels (2 uninfected, 7 with past, and 11 with ongoing infection with GSHV) and in 11 HCCs from woodchucks persistently infected with woodchuck hepatitis virus. Five GSHV carrier and two uninfected ground squirrels received i.p. administration of aflatoxin B1. We detected only one mutation in the p53 gene of the tested animals. This mutation was located in codon 176 of exon 5 in the HCC of a GSHV-positive ground squirrel treated with aflatoxin. Mutation was caused by a G to T transversion in the second position of the codon, resulting in the replacement of cysteine with phenylalanine, and was accompanied by a tumor-specific loss of heterozygosity. p53 allelic amino acid variation with sequences coding for aspartic acid or asparagine was present in codon 61 in the variable region of exon 4 in both HCCs and nonneoplastic tissues of ground squirrels. In view of the considerably lower apparent rate of mutations in comparison to human HCCs, we suggest a less important role for aflatoxin in the induction of p53 mutations in HCCs of ground squirrels. Alternatively, etiological factors other than p53 mutations may be of greater significance in the development of HCC in ground squirrels and woodchucks.
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PMID:State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. 792 76

The effect of feeding mycotoxins, i.e. aflatoxin B1 (1.25 ppm from 3 to 38 days of age) and ochratoxin A (0.5 ppm from 3 to 38 days of age) along with inclusion body hepatitis virus (IBHV) inoculation (at 10 days of age) singly and in combination was studied in broiler chicks. Birds in combined treatment groups, i.e. aflatoxin fed and virus inoculated and ochratoxin fed and virus inoculated, showed more changes in activities of phosphatases (AKPase, ATPase, G-6-Pase and ACPase) in liver and kidney tissues than their respective individual treatment groups with a few exceptions. Reduction in the activities of oxido-reductases in liver and kidney tissues were almost comparable in different treatment groups. The increase in muco-polysaccharides reaction was more marked in both the combined treatment groups than the single treatment groups. Intensity of lipid reaction was more in ochratoxin virus combination group than either alone.
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PMID:Histochemical/histoenzymic studies in broiler chicks fed aflatoxin, ochratoxin and inoculated with inclusion body hepatitis virus singly and in concurrence. 802 44

The expression of 14 forms of cytochrome P450 in the liver as well as changes in the testosterone hydroxylation activities of hepatic microsomes were investigated during the development of hepatitis in Long-Evans Cinnamon (LEC) rats. P4501A1 and -1A2 (3-methylcholanthrene-inducible forms) and P4502B1 and -2B2 (phenobarbital-inducible forms) were barely detected in the hepatic microsomes of male and female LEC rats. In immature male rats, the levels of male-specific forms (P4502C11 and -2C13) were higher in LEC rats than in control Long-Evans Agouti (LEA) rats. P4502C11 appeared in female LEC rats from 4 to 16 weeks of age, reflecting that testosterone 2 alpha- and 16 alpha-hydroxylation activities were detected at significant levels in female LEC rats. In immature female rats, the level of P4502C12 (a major female-specific form) was higher in LEC rats than in LEA rats. The level of P4502C13 in male LEC rats and that of P4502C12 in female LEC rats decreased markedly with ageing or during the development of hepatitis. The level of P4503A2 (a male-predominant form) was especially high in immature male and female LEC rats, reflecting that both rats had high 2 beta- and 6 beta-hydroxylation activities toward testosterone. These sex-specific forms are regulated by androgens and by pituitary growth hormone. Thus, there may be abnormalities of the hypothalamo-pituitary-gonadal axis in LEC rats. Furthermore, P4503A2 efficiently activates aflatoxin B1, a potent hepatocarcinogen, and the increased levels of this form in LEC rats may be related to the onset of hepatitis or liver cancer.
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PMID:Expression of cytochrome P450 in LEC rats during the development of hereditary hepatitis and hepatoma. 842 59

Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly, the mortality rates in 1990 (per 100,000) were 20.10 in certain cities and 24.32 in certain counties. More than 90% of HCC cases and 70% of controls were infected with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10-50). In the same group of patients, 8-27% of those with HCC and 0-11% of the healthy controls were also infected with hepatitis C (HCV) (OR = 2.11-17.29). There appears to be some correlation between HBV markers and the OR. The government requires that 85% of infants be immunized with HBV vaccine. In 1992, there were 3 million infants inoculated with HB vaccines. Aflatoxins have been found as contaminants in food, particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake of aflatoxin B1 (AFB1) by people of ten different villages correlated with HCC mortality rates (r = 0.55; P < 0.05). The concentration of AFB1-albumin adducts is an indicator of individual exposure to aflatoxins. These adducts are higher in hyperendemic HCC areas and cases. Most people have now changed their staple food and eat rice instead of corn. Six large epidemiological studies have confirmed that people who drink pond-ditch water experience higher HCC mortality rates than people who drink deep-well water. Recent research has found that the blue-green algal toxin microcystin (MCYST) was a contaminant of pond-ditch water. MCYST is a strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver necrosis. More than 80% of people in Qidong County have already changed their sources of water from pond-ditches to deep wells. Therefore, a combined strategy of the prevention of hepatitis, control of crops and control of drinking water is advocated for the primary prevention of HCC in China.
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PMID:Primary prevention of hepatocellular carcinoma. 858 Apr 13

The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.
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PMID:An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico. 864 Sep 5

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